ArticleNature communications2021
WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Structural basis of Ku-mediated activation of WRN exonuclease activity.Nature communications · 2026Article
- Rare genetic diseases associated with G-quadruplex-induced replication stress.Communications biology · 2026Review
- The bacterial MRE11-RAD50 and DNA2-WRN homologs process replication forks at distinct and separate loci on the chromosome.FEBS letters · 2026Article
- Pan-Cancer Analysis of WRN: From Multi-Omics Biomarker Discovery to Therapy-Guiding Functional Evidence.OncoTargets and therapy · 2026Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Cytosolic DNA and intracellular CaDNA repair · 2025Review
- Quinazoline Derivative kzl052 Suppresses Prostate Cancer by Targeting WRN Helicase to Stabilize DNA Replication Forks.International journal of molecular sciences · 2025Article
- Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR.Nature communications · 2025Article
- Novel De NovoInternational journal of molecular sciences · 2025Article
- To cleave or not and how? The DNA exonucleases and endonucleases in immunity.Genes & diseases · 2025Review
- Phosphorylation-dependent WRN-RPA interaction promotes recovery of stalled forks at secondary DNA structure.Nature communications · 2025Article
- Development of a Prognostic Risk Model Based on Oxidative Stress-related Genes for Platinum-resistant Ovarian Cancer Patients.Recent patents on anti-cancer drug discovery · 2025Article
- USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.Nature communications · 2024Article
- Replication stress as a driver of cellular senescence and aging.Communications biology · 2024Review
- Genome maintenance meets mechanobiology.Chromosoma · 2024Review
- New Facets of DNA Double Strand Break Repair: Radiation Dose as Key Determinant of HR versus c-NHEJ Engagement.International journal of molecular sciences · 2023Review
- A new wave of innovations within the DNA damage response.Signal transduction and targeted therapy · 2023Review
- Review
- PHOSPHORYLATION-DEPENDENT ASSOCIATION OF WRN WITH RPA IS REQUIRED FOR RECOVERY OF REPLICATION FORKS STALLED AT SECONDARY DNA STRUCTURES.bioRxiv : the preprint server for biology · 2023Article
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The tumor suppressor BRCA2 protects stalled forks from degradation to maintain genome stability. However, the molecular mechanism(s) whereby unprotected forks are stabilized remains to be fully characterized. Here, we demonstrate that WRN helicase ensures efficient restart and limits excessive degradation of stalled forks in BRCA2-deficient cancer cells. In vitro, WRN ATPase/helicase catalyzes fork restoration and curtails MRE11 nuclease activity on regressed forks. We show that WRN helicase inhibitor traps WRN on chromatin leading to rapid fork stalling and nucleolytic degradation of unprotected forks by MRE11, resulting in MUS81-dependent double-strand breaks, elevated non-homologous end-joining and chromosomal instability. WRN helicase inhibition reduces viability of BRCA2-deficient cells and potentiates cytotoxicity of a poly (ADP)ribose polymerase (PARP) inhibitor. Furthermore, BRCA2-deficient xenograft tumors in mice exhibited increased DNA damage and growth inhibition when treated with WRN helicase inhibitor. This work provides mechanistic insight into stalled fork stabilization by WRN helicase when BRCA2 is deficient.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.